Phase III Randomized Comparison of Gemcitabine Versus Gemcitabine plus Capecitabine in Patients with Advanced Pancreatic Cancer

The authors assessed the incidence, management, and risk factors for postoperative complications after right lobe (RL) live donor hepatectomy in a high-volume center in North America. All donors undergoing an RL live donor hepatectomy between 2000 and 2017 at our institution were included. The primary outcome was the development of complications (both medical and surgical). Predictors of postoperative complications were determined by logistic regression. A total of 587 patients underwent RL live donor hepatectomy. Among those, 187 postoperative complications were diagnosed in 141 (24%) patients. One patient had >90-day morbidity, and there were no donor deaths. Overall complications were significantly higher in the first era, 2000 to 2008 (81 [57.4%]) versus the second era, 2009 to 2017 (60 [42.6%]) (p = 0.01). On multivariate analysis, the only predictor of postoperative complications was the center volume of RL live donor hepatectomy in the previous 12 months with an odds ratio of 0.97 (95% confidence interval: 0.95–0.99). In conclusion, increasing center volume is associated with lower rates of postoperative complications after RL living liver donation.

Surgical Complications after Right Hepatectomy for Live Liver Donation: Largest Single-Center Western World Experience.

BACKGROUND Data on liver transplantation (LT) in acute on chronic liver failure (ACLF) are scanty. AIM To perform meta-analysis on outcomes after LT for ACLF compared with ACLF patients not receiving LT or with LT recipients for indications other than ACLF. METHODS We pooled data from 12 studies on LT outcomes among ACLF patients. RESULTS Among nine studies, 22 238 LT recipients for ACLF vs 30 791 for non-ACLF were younger by 1.1 years, less males (64% vs 66.4%), and higher model for end-stage disease score by 14.5 (14.4-14.6), P < 0.01 for all. Post-transplant patient survival at 30 day, 90 day, 6 months, 1 year and 5 years was lower in ACLF: 96.2% vs 98.1%, 92.6% vs 96.2%, 89.9% vs 94.4%, 86.0% vs 91.9%, 66.9% vs 80.7% respectively, P < 0.01 for all. ACLF patients stayed longer in hospital and ICU by 5.7 and 10.5 days respectively, P < 0.001, with similar post-transplant complications [74.4% vs 55.5%, P = 0.12]. Among three studies, 441 LT recipients for ACLF vs 301 ACLF patients not selected for LT had better 30 day and 1 year survival: 95.2% vs 60% and 85.3% vs 28.2% respectively, P < 0.001. Outcomes were worse in ACLF-3 and better for ACLF-1 and ACLF-2 patients at the time of LT. CONCLUSION In this pooled analysis with a large sample size across the globe, LT for select patients with ACLF provided survival benefit. However, larger prospective studies are needed to further refine selection criteria, especially for ACLF-3 patients as basis for improving outcomes and optimal utilisation of scarce donor pool.

Systematic review with meta-analysis: liver transplant provides survival benefit in patients with acute on chronic liver failure.

The Failure to Rescue (FTR) rate is defined as the mortality rate among patients who experience one or more complications. It has been used as an outcome metric for approximately 25 years, primarily in elective surgery populations, and has been shown to be associated with factors that are modifiable on the institutional level. Although the FTR metric was derived in elective surgical populations, modifications have been made in attempts to refine the metric and apply it to broader populations, including medical patients and non-elective surgical patients. However, study among emergency general surgery patients has been limited. In this review, we summarize the current knowledge surrounding FTR, including established risk factors and potential limitations of the metric in emergency general surgery (EGS) populations. We then discuss a conceptual model for FTR events and review strategies to minimize rates. Finally, we provide a brief overview of current areas of study and potential future directions in acute care surgery.

Failure to rescue in surgical patients: A review for acute care surgeons.

Liver transplantation (LT) has revolutionized outcomes for cirrhotic patients. Current liver allocation policies dictate patients with highest short-term mortality receive the highest priority, thus, several patients become increasingly ill on the waitlist. Given cirrhosis is a progressive disease, it can be complicated by the occurrence of acute-on-chronic liver failure (ACLF), a syndrome defined by an acute deterioration of liver function associated with extrahepatic organ failures requiring intensive care support and a high short-term mortality. Successfully bridging to transplant includes accurate prognostication and prioritization of ACLF patients awaiting LT, optimizing intensive care support pre-LT, and tailoring immunosuppressive and anti-infective therapies post-LT. Furthermore, predicting futility (too sick to undergo LT) in ACLF is challenging. In this review, we summarize the role of LT in ACLF specifically highlighting (a) current prognostic scores in ACLF, (b) critical care management of the ACLF patient awaiting LT, (c) donor issues to consider in transplant in ACLF, and (d) exploring of recent post-LT outcomes in ACLF and potential opportunities to improve outcomes including current care gaps and unmet research needs.

Liver Transplantation in Acute-on-chronic Liver Failure.

There is paucity of data on intermediate-term post liver transplant outcomes from South Asia. The objective of this study was to determine survival outcomes in patients who underwent living donor liver transplantation (LDLT) in a busy liver transplant center in Pakistan. This study was a review of patients who underwent LDLT between 2012 and 2016. A total of 321 patients were included in this study. Early (within 90 days) and late (>90 days) morbidity and mortality was assessed. Estimated 1- and 4-year survival was determined. Median age was 48 (18–73) years. Male to female ratio was 4.5:1. Out of total 346 complications, 184 (57.3%) patients developed 276 (79.7%) complications in early post-transplant period, whereas there were 70 (21.3%) late complications. Most common early complication was pleural effusion in 46 (16.6%) patients. Biliary complications were the most common late complication and were seen in 31/70 (44.2%) patients. Overall 21.4% patients had a biliary complication. The 3-month mortality was 14%. The estimated 1- and 4-year OS for a MELD cutoff of 30 was 84.5 versus 72 and 80 versus 57% (P = 0.01). There was no donor mortality. Acceptable intermediate-term post-transplant outcomes were achieved with LDLT. There is a need to improve outcomes in high-MELD patients.

Living Donor Liver Transplantation in South Asia: Single Center Experience on Intermediate-Term Outcomes

Background The European association for the study of the liver and chronic liver failure consortium (EASL-CLIF) recently proposed diagnostic criteria for acute on chronic liver failure (ACLF). There is lack of data regarding liver transplant outcomes in ACLF patients based on these criteria. The objective of this study was to determine outcome following living donor liver transplantation (LDLT) in ACLF patients. Methods We retrospectively reviewed patients who underwent LDLT for ACLF based on European association for the study of the liver and chronic liver failure consortium (EASL-CLIF) diagnostic criteria (group 1) (N = 60) and compared them with ACLF patients who did not undergo transplantation (group 2) (N = 59). The primary outcome of interest was 30 day mortality. We also looked at one year survival in these patients. Survival was calculated using Kaplan–Meier curves and Log rank test was used to determine significance between variables. Results Median MELD scores for group 1 and 2 patients in ACLF grade 1 was 28 (20–38) and 31 (24–36), in ACLF grade 2 was 35 (24–42) and 36 (24–42) and in ACLF grade 3 was 36 (29–42) and 38 (32–52). For group 1 and 2, 30 day mortality in ACLF grade 1, 2 and 3 was 2/43(4.6%) versus 9/15(60%) (P  Conclusion LDLT has excellent outcomes in patients with EASL-CLIF grade 1 and 2 ACLF. Without transplantation, ACLF patients have a very poor prognosis.

Living Donor Liver Transplantation for Acute on Chronic Liver Failure Based on EASL-CLIF Diagnostic Criteria

Survival advantage with para aortic lymphadenectomy in peri-ampullary cancer: A retrospective cohort study

Background Living donor liver transplantation (LDLT) is an established treatment for patients with cirrhosis and hepatocellular carcinoma (HCC) within Milan criteria. Acceptable outcomes have been demonstrated in patients fulfilling extended criteria. Here, we share our experience with LDLT for patients with HCC within and beyond Milan criteria, with emphasis on poor prognostic factors. Methods We retrospectively reviewed patients who underwent LDLT between 2012 and 2017 and had HCC proven on explant liver histopathology. A total of 117 patients were included. Patients who died early after transplant (in 600, (2) poor differentiation, and (3) the presence of lymphovascular invasion. Recurrence-free survival (RFS) was determined using Kaplan–Meier curves. Results Median age was 53 (30–73) years. Median follow-up was 20.3 (1–63.2) months. Median model for end stage liver disease (MELD) score was 19 (9–34). Of a total of 117 patients, 74 (63.2%) patients met Milan criteria. Recurrence rate was 12/117 (10.3%). Actuarial 5-year RFS was 88% and 82% (P = 0.3) in patients within and outside Milan criteria. There was no difference in 3-year RFS in patients with 0, 1, or 2 poor prognostic factors within Milan criteria (92%, 87%, and 75%, respectively; P = 0.3). However, a significant difference in RFS was seen in patients outside Milan criteria (92%, 93%, and 53%; P = 0.03). Conclusions Patients within Milan criteria have acceptable RFS even in the presence of poor prognostic factors. However, the presence of two or more poor prognostic variables significantly impacts RFS of patients outside Milan criteria.

Living Donor Liver Transplantation for Hepatocellular Carcinoma: A Single-Center Experience from Pakistan.

Living donor liver transplantation (LDLT) is an acceptable treatment option for hepatocellular carcinoma (HCC). Traditional transplant criteria aim at best utilization of donor organs with low risk of post transplant recurrence. In LDLT, long term recurrence free survival (RFS) of 50% is considered acceptable. The objective of the current study was to determine preoperative factors associated with high recurrence rates in LDLT. Between April 2012 and December 2019, 898 LDLTs were performed at our center. Out of these, 242 were confirmed to have HCC on explant histopathology. We looked at preoperative factors associated with ≤ 50%RFS at 4 years. For survival analysis, Kaplan Meier curves were used and Cox regression analysis was used to identify independent predictors of recurrence. Median AFP was 14.4(0.7–11,326.7) ng/ml. Median tumor size was 2.8(range = 0.1–11) cm and tumor number was 2(range = 1–15). On multivariate analysis, AFP > 600 ng/ml [HR:6, CI: 1.9–18.4, P = 0.002] and microvascular invasion (MVI) [HR:5.8, CI: 2.5–13.4, P   600 ng/ml, MVI was seen in 88.9% tumors with poor grade and 75% of tumors outside University of California San Francisco criteria. Estimated 4 year RFS was 78% for the entire cohort. When AFP was  600 ng/ml, RFS was 53% and 0 with well-moderate and poor grade tumors respectively (P   600 ng/ml, a preoperative biopsy to rule out poor differentiation should be considered for patient selection.

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Nusrat Yar Khan

Papers

Living Donor Liver Transplantation in South Asia: Single Center Experience on Intermediate-Term Outcomes

Living Donor Liver Transplantation for Acute on Chronic Liver Failure Based on EASL-CLIF Diagnostic Criteria

Survival advantage with para aortic lymphadenectomy in peri-ampullary cancer: A retrospective cohort study

Living Donor Liver Transplantation for Hepatocellular Carcinoma: A Single-Center Experience from Pakistan.

When to call it off: defining transplant candidacy limits in liver donor liver transplantation for hepatocellular carcinoma.